This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite ongoing control and prevention efforts, malaria remains one of the most devastating infectious diseases, world-wide. Female Anopheles mosquitoes are the vectors for human malaria. When a mosquito bites an infected individual, it takes up infectious forms of the parasite along with blood. The parasite undergoes a complex journey through its mosquito vector, before it can subsequently be injected into the next human host via mosquito bite. As part of this journey, the parasite must cross two epithelia, the mosquitoes'midgut and the salivary glands This study aims to characterize a common mosquito epithelial immune response against malaria parasite invasion, which is characterized by the serine protease inhibitor serpin-6 (SRPN6). Our aims are to (a) explore the regulation of SRPN6 during the invasion of the midgut and salivary glands by the parasite and (b) to measure any potential effect of SRPN6 on the passage of the parasite through these epithelia. The results of this study can provide important clues to the potential contribution of epithelial immunity to parasite transmission by mosquito vectors in a disease-relevant mosquito/parasite combination.